Omega-3 fatty acids are a major constituent of photoreceptor and neural membranes as well as precursors of prostaglandins and other eicosanoids. Our previous studies of rhesus monkeys demonstrated that diets low in omega-3 fatty acids during gestation and infancy led to reduced levels in the brain and retina, deficits in retinal function, slower visual acuity development and changes in visual attention. All of these findings were confirmed in human infants and led to increased omega-3 fatty acids in human infant formulas. We are now examining the effects of different dietary levels and sources of omega-3 fatty acids on immune system function. We compared three groups of rhesus monkeys raised on diets low in linolenic acid (18:3w3), high in linolenic acid, or supplemented with the longer-chain omega-3 fatty acid, docosahexaenoic acid (DHA, 22:6w3), which is found in primate milk but not in current US infant formulas. Immune system function was evaluated for several weeks before and after the unavoidable stress of a change in the animals' housing room. The number and proportion of neutrophils, total lymphocytes, and CD4+, CD8+ and CD20+ lymphocyte subsets were determined by differential cell counts and flow cytometry, and response to a T-lymphocyte mitogen, phytohemagglutinin (PHA), was measured in blood samples from the three groups. Over all timepoints, animals fed DHA had a significantly lower response to PHA than animals fed either low or high levels of linolenic acid. In addition, DHA-supplemented animals had a significantly higher proportion of CD8+ lymphocytes (suppressor/cytotoxic T-lymphocytes), and a lower CD4+/CD8+ ratio, than animals fed the high linolenic acid diet. All diet groups showed immune system changes in response to the move, but they did not respond differentially. We explored possible relationships between these findings and the incidence of illness, specifically minor gastrointestinal infections which are common in macaque monkeys. DHA-supplemented animals had a significantly lower incidence of gastrointestinal parasitic infections in the first 4 postnatal months. These results suggest that DHA supplementation may reduce inflammatory responses and thereby ameliorate some disease processes. Such effects have been found in adults fed high levels of omega-3 fatty acids, but have not been demonstrated previously in infants with the DHA levels now being considered for human infant feeding. We are attempting to confirm this finding and explore its underlying mechanisms.